P09110 (THIK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
3-ketoacyl-CoA thiolase, peroxisomal
EC=2.3.1.16

Alternative name(s):
Acetyl-CoA acyltransferase
Beta-ketothiolase
Peroxisomal 3-oxoacyl-CoA thiolase

Gene names

Name:	ACAA1
Synonyms:	ACAA, PTHIO

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	424 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Catalytic activity	Acyl-CoA + acetyl-CoA = CoA + 3-oxoacyl-CoA.
Pathway	Lipid metabolism; fatty acid metabolism.
Subunit structure	Homodimer. Ref.10
Subcellular location	Peroxisome.
Induction	Peroxisomal thiolase is markedly induced (at the level of transcription) by various hypolipidemic compounds in parallel with the other two enzymes of the peroxisomal beta-oxidation system.
Sequence similarities	Belongs to the thiolase family.

Ontologies

Keywords
Biological process	Fatty acid metabolism Lipid metabolism
Cellular component	Peroxisome
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transit peptide
Molecular function	Acyltransferase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	alpha-linolenic acid metabolic process Traceable author statement. Source: Reactome bile acid metabolic process Inferred from mutant phenotype PubMed 2318981. Source: UniProtKB fatty acid beta-oxidation using acyl-CoA oxidase Traceable author statement. Source: Reactome very long-chain fatty acid metabolic process Inferred from mutant phenotype PubMed 2318981. Source: UniProtKB
Cellular_component	peroxisomal matrix Traceable author statement. Source: Reactome
Molecular_function	acetyl-CoA C-acyltransferase activity Inferred from electronic annotation. Source: EC palmitoyl-CoA oxidase activity Inferred from mutant phenotype PubMed 2882519. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P09110-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P09110-2)

The sequence of this isoform differs from the canonical sequence as follows:
     149-181: Missing.
     272-331: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 26

26

Peroxisome

Chain

27 – 424

398

3-ketoacyl-CoA thiolase, peroxisomal

PRO_0000034067

Sites

Active site

123

1

Acyl-thioester intermediate By similarity

Active site

377

1

Proton acceptor By similarity

Active site

408

1

Proton acceptor By similarity

Amino acid modifications

Modified residue

59

1

Phosphothreonine Ref.8

Modified residue

60

1

Phosphothreonine Ref.8

Natural variations

Alternative sequence

149 – 181

33

Missing in isoform 2.

VSP_046195

Alternative sequence

272 – 331

60

Missing in isoform 2.

VSP_046196

Natural variant

172

1

E → D.
Corresponds to variant rs156265 [ dbSNP | Ensembl ].

VAR_011904

Natural variant

387

1

V → A. Ref.7
Corresponds to variant rs2229528 [ dbSNP | Ensembl ].

VAR_069148

Secondary structure

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424

Helix Strand Turn

Details...

Beta strand

38 – 45

8

Turn

51 – 53

3

Turn

55 – 58

4

Helix

61 – 76

16

Helix

80 – 82

3

Beta strand

86 – 89

4

Beta strand

91 – 94

4

Helix

95 – 97

3

Helix

98 – 107

10

Beta strand

116 – 120

5

Helix

122 – 124

3

Helix

125 – 138

14

Beta strand

143 – 152

10

Turn

153 – 155

3

Helix

168 – 170

3

Helix

172 – 175

4

Helix

176 – 178

3

Helix

181 – 191

11

Helix

196 – 216

21

Turn

217 – 222

6

Beta strand

226 – 231

6

Beta strand

237 – 242

6

Helix

254 – 259

6

Beta strand

263 – 265

3

Beta strand

279 – 289

11

Helix

290 – 296

7

Beta strand

302 – 311

10

Helix

314 – 319

6

Helix

320 – 332

13

Helix

336 – 338

3

Beta strand

339 – 344

6

Helix

349 – 359

11

Helix

363 – 365

3

Helix

372 – 375

4

Turn

379 – 381

3

Helix

382 – 397

16

Beta strand

401 – 409

9

Turn

410 – 412

3

Beta strand

413 – 421

9

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 1989. Version 2. Checksum: 71B2BBAFA06AE412	FASTA	424	44,292
	10 20 30 40 50 60 MQRLQVVLGH LRGPADSGWM PQAAPCLSGA PQASAADVVV VHGRRTAICR AGRGGFKDTT 70 80 90 100 110 120 PDELLSAVMT AVLKDVNLRP EQLGDICVGN VLQPGAGAIM ARIAQFLSDI PETVPLSTVN 130 140 150 160 170 180 RQCSSGLQAV ASIAGGIRNG SYDIGMACGV ESMSLADRGN PGNITSRLME KEKARDCLIP 190 200 210 220 230 240 MGITSENVAE RFGISREKQD TFALASQQKA ARAQSKGCFQ AEIVPVTTTV HDDKGTKRSI 250 260 270 280 290 300 TVTQDEGIRP STTMEGLAKL KPAFKKDGST TAGNSSQVSD GAAAILLARR SKAEELGLPI 310 320 330 340 350 360 LGVLRSYAVV GVPPDIMGIG PAYAIPVALQ KAGLTVSDVD IFEINEAFAS QAAYCVEKLR 370 380 390 400 410 420 LPPEKVNPLG GAVALGHPLG CTGARQVITL LNELKRRGKR AYGVVSMCIG TGMGAAAVFE YPGN
	Isoform 2 [UniParc]. Checksum: 8137A0AC448FBA24	FASTA	331	34,665
	10 20 30 40 50 60 MQRLQVVLGH LRGPADSGWM PQAAPCLSGA PQASAADVVV VHGRRTAICR AGRGGFKDTT 70 80 90 100 110 120 PDELLSAVMT AVLKDVNLRP EQLGDICVGN VLQPGAGAIM ARIAQFLSDI PETVPLSTVN 130 140 150 160 170 180 RQCSSGLQAV ASIAGGIRNG SYDIGMACGI TSENVAERFG ISREKQDTFA LASQQKAARA 190 200 210 220 230 240 QSKGCFQAEI VPVTTTVHDD KGTKRSITVT QDEGIRPSTT MEGLAKLKPA FKKDGSTTAG 250 260 270 280 290 300 LTVSDVDIFE INEAFASQAA YCVEKLRLPP EKVNPLGGAV ALGHPLGCTG ARQVITLLNE 310 320 330 LKRRGKRAYG VVSMCIGTGM GAAAVFEYPG N

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nucleotide sequence of human peroxisomal 3-oxoacyl-CoA thiolase." Bout A., Teunissen Y., Hashimoto T., Benne R., Tager J.M. Nucleic Acids Res. 16:10369-10369(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Liver.
[2]	Bout A. Submitted (AUG-1989) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION TO 285-287.
[3]	"Complete cDNA sequence of human foetal liver peroxisomal 3-oxoacyl-CoA thiolase." Fairbairn L.J., Tanner M.J.A. Nucleic Acids Res. 17:3588-3588(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Liver.
[4]	"Characterization of the gene encoding human peroxisomal 3-oxoacyl-CoA thiolase (ACAA). No large DNA rearrangement in a thiolase-deficient patient." Bout A., Franse M.M., Collins J., Blonden L., Tager J.M., Benne R. Biochim. Biophys. Acta 1090:43-51(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT ALA-387. Tissue: Lymph, Ovary and Pancreas.
[8]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-59 AND THR-60, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[9]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]	"Crystal structure of human peroxisomal acetyl-COA acyl transferase 1 (ACAA1)." Structural genomics consortium (SGC) Submitted (OCT-2006) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 28-424, SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X12966 mRNA. Translation: CAA31412.1.
X14813 mRNA. Translation: CAA32918.1.
X65140 Genomic DNA. Translation: CAA46270.1.
X65148 Genomic DNA. Translation: CAA46271.1.
AP006309 Genomic DNA. No translation available.
CH471055 Genomic DNA. Translation: EAW64516.1.
BC000635 mRNA. Translation: AAH00635.1.
BC011977 mRNA. Translation: AAH11977.1.
BC014474 mRNA. Translation: AAH14474.1.

IPI

IPI00012828.
IPI00303933.

PIR

XUHUAB. S17515.

RefSeq

NP_001123882.1. NM_001130410.1.
NP_001598.1. NM_001607.3.

UniGene

Hs.643487.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2IIK	X-ray	2.55	A/B	30-423	[»]

ProteinModelPortal

P09110.

ModBase

Search...

Protein-protein interaction databases

IntAct

P09110. 1 interaction.

STRING

9606.ENSP00000333664.

PTM databases

PhosphoSite

P09110.

Polymorphism databases

DMDM

135751.

2D gel databases

REPRODUCTION-2DPAGE

IPI00012828.

UCD-2DPAGE

P09110.

Proteomic databases

PaxDb

P09110.

PeptideAtlas

P09110.

PRIDE

P09110.

Protocols and materials databases

DNASU

30.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000301810; ENSP00000301810; ENSG00000060971.
ENST00000333167; ENSP00000333664; ENSG00000060971.

GeneID

30.

KEGG

hsa:30.

UCSC

uc003cht.3. human.

Organism-specific databases

CTD

30.

GeneCards

GC03M038164.

HGNC

HGNC:82. ACAA1.

HPA

HPA006764.
HPA007244.

MIM

604054. gene.

neXtProt

NX_P09110.

PharmGKB

PA24419.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0183.

HOGENOM

HOG000012239.

HOVERGEN

HBG003112.

InParanoid

P09110.

KO

K07513.

OMA

AAYQRTS.

OrthoDB

EOG45QHDC.

PhylomeDB

P09110.

Enzyme and pathway databases

BioCyc

MetaCyc:HS00752-MONOMER.

Reactome

REACT_111217. Metabolism.

UniPathway

UPA00199.

Gene expression databases

ArrayExpress

P09110.

Bgee

P09110.

CleanEx

HS_ACAA1.

Genevestigator

P09110.

GermOnline

ENSG00000060971. Homo sapiens.

Family and domain databases

Gene3D

3.40.47.10. 2 hits.

InterPro

IPR002155. Thiolase.
IPR016039. Thiolase-like.
IPR016038. Thiolase-like_subgr.
IPR020615. Thiolase_acyl_enz_int_AS.
IPR020610. Thiolase_AS.
IPR020617. Thiolase_C.
IPR020613. Thiolase_CS.
IPR020616. Thiolase_N.
[Graphical view]

PANTHER

PTHR18919. PTHR18919. 1 hit.

Pfam

PF02803. Thiolase_C. 1 hit.
PF00108. Thiolase_N. 1 hit.
[Graphical view]

PIRSF

PIRSF000429. Ac-CoA_Ac_transf. 1 hit.

SUPFAM

SSF53901. Thiolase-like. 2 hits.

TIGRFAMs

TIGR01930. AcCoA-C-Actrans. 1 hit.

PROSITE

PS00098. THIOLASE_1. 1 hit.
PS00737. THIOLASE_2. 1 hit.
PS00099. THIOLASE_3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

ACAA1. human.

EvolutionaryTrace

P09110.

GenomeRNAi

30.

NextBio

107.

SOURCE

Search...

Entry information

Entry name

THIK_HUMAN

Accession

Primary (citable) accession number: P09110
Secondary accession number(s): G5E935, Q96CA6

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	October 1, 1989
Last modified:	May 1, 2013
This is version 153 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.